心肾综合征的中西医机制研究进展

心力衰竭(心衰)和肾功能不全是临床上常见的综合征.据报道[1],在因急性心力衰竭入院的患者中,19％～45％的患者出现了肾功能恶化.心力衰竭(heart failure HF)患者出现肾功能不全或使原有的肾功能不全进行性加重,即心肾综合征( cardiorenal syndrome,CRS).近年来,CRS日益引起临床医生的关注.依据其临床表现,中医多将CRS归属于水气病、心悸、喘促、胸痹、痰饮、水肿等范畴.心脏与肾脏相互影响、互相作用导致恶性循环,进一步加速了多器官的功能衰竭,使病死率增加.目前对于CRS的认识还十分有限,是临床处理的棘手问题.本文将分别从中、西医角度对心肾综合征相关机制予以阐述.     

2012年第1期中文目录

心肾综合征特指在心力衰竭的治疗过程中,由于患者的肾功能出现明显下降,而导致心力衰竭治疗效果欠佳.目前,其诊断尚无统一标准,有学者将诊断标准确定为,在急性心力衰竭时血清肌酐升高3.0～5.0 mg/dl或者肾小球滤过率下降15 ml/min以上.心肾综合征确切发病率仍不清楚,但有研究显示,其在心力衰竭患者中的发病率可达30％左右.心肾综合征的病理生理机制比较复杂,中心静脉淤血、神经内分泌激活、贫血、氧化应激和肾交感神经过度激活可能是导致心肾综合征的重要原因.心肾综合征的治疗仍是一个很大的难题.原则上首先应纠正心肾综合征的可逆性诱因;其次,需要确定患者肾灌注状态,保证收缩压在80mmHg以上,平均压在60mmHg以上,对于低心排血量患者,可尝试使用硝酸酯类药物,降低心脏前后负荷;此外,还需及时停用影响肾功能的药物.具体讲,利尿剂、血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂、血液滤过、重组人B型利钠肽和加压素拮抗剂均可考虑应用.本文就心肾综合征的上述相关问题做一综述.     

腹膜透析在心肾综合征治疗中的应用

心肾综合征(CRS)的治疗难点在于心肾功能障碍的交织,心功能不全导致肾功能损伤,肾功能不全加重心功能不全恶化。其共同病理生理学特点使得纠正高容量负荷成为行之有效的治疗方法,如利尿剂和血液滤过治疗等,但都存在局限性,而腹膜透析(PD)则可提供安全有效的超滤。本文拟简介PD治疗心肾综合征的理论基础与临床实践。     

老年人心肾贫血综合征研究进展

心肾贫血综合征是Silverberg提出的一个新概念,其基本病理生理学机制是充血性心力衰竭、慢性肾功能不全和贫血之间存在恶性循环。值得重视的是Silverberg等对心肾贫血综合征患者采取皮下注射红细胞生成素和静脉注射铁剂并用的方法,显著地提高了患者的心功能,明显地降低了患者的死亡率。本文就其研究进展作一综述。     

肾功能不全并发心力衰竭的诊治策略

肾功能衰竭和心力衰竭常并存,可以互为因果,临床上称此状态为心肾综合征。心肾综合征共分五类,其中3型和4型心肾综合征分别由急性和慢性肾功能不全导致的心力衰竭。我院对一组心力衰竭患者的回顾性分析表明,肾功能不     

心肾综合征的临床研究进展

心肾综合征一词已广泛用于进行性充血性心力衰竭引起的肾功能下降。为了概括心脏与肾脏之间复杂的因果关系,心肾综合征分为5种临床亚型:Ⅰ型:急性心肾综合征;Ⅱ型:慢性心肾综合征;Ⅲ型:急性肾心综合征;Ⅳ型:慢性肾心综合征;Ⅴ型:继发性心肾综合征。心肾综合征是慢性肾功能不全和慢性心力衰竭中治疗的难题,现就心肾综合征近年来临床研究进展进行综述。     

心肾贫血综合征

心脏与肾脏之间存在着密切的交互作用,使得心肾综合征在临床中并不少见。贫血不仅是慢性肾脏病的重要 并发症之一,在心力衰竭患者中亦非常常见,因此称之为心肾贫血综合征。贫血会显著增加心力衰竭患者住院和死 亡风险,并促进肾脏病进展,增加肾脏替代治疗的风险。在心肾贫血综合征的发病机制中,促红细胞生成素缺乏及铁 缺乏等均起到了关键作用。因此,对于心肾贫血综合征的治疗也应重视促红细胞生成素的补充、低氧诱导因子-脯 氨酰羟化酶抑制剂（HIF-PHI）及补铁治疗。目前在心肾贫血综合征的发病机制及治疗方面仍有很多问题尚未解决, 需要更多的基础与临床研究提供强有力的证据。     

心肾综合征治疗分析

近年来慢性心力衰竭病人出现肾功能不全即心肾综合征的问题，逐渐引起人们的注意。广义的心肾综合征是指心脏和肾脏中的一个器官对另一个器官的共同损害。狭义的心肾综合征是特指慢性心力衰竭引起的进行性肾脏损害，并导致肾功能不全，通常认为是慢性心力衰竭的终末期的一种表现。近年来，随着老年化社会的逐步形成和人民生活水平的提高，慢性心血管病（如高血压、冠心病）和代谢紊乱性疾病（如糖尿病、高脂血症、高尿酸血症）的发病率明显升高，内外科治疗的进展使许多心血管疾病病人在疾病的急性期得到了有效的治疗，病情发展到终末期的病人也明显增加，并常存在肾功能不全，出现心肾综合征，预后差。现将湖北省当阳市长坂坡医院2001年-2005年收治的40例心肾综合征病人分析报道如下。     

心肾综合征的最新进展

心脏和肾脏之间的关系越来越得到医学界的广泛关注,心力衰竭与肾功能衰竭常常合并存在并相互影响,互为因果,这两者共存的情况称为心肾综合征.心肾综合征的病理生理学机制极为复杂,迄今尚未阐明.当心力衰竭与肾功能衰竭两者并存时,不仅处理困难,而且预后亦差.现着重对于心肾综合征的最新研究进展、治疗策略方面进行讨论.     

老年慢性心力衰竭患者贫血与肾功能障碍的关系

目的探讨贫血对老年慢性心力衰竭（CHF）病情及预后的影响。方法老年CHF患者118例,按血红蛋白水平将其分为轻度贫血组、中度贫血组和重度贫血组,采用前瞻性队列研究的方法,在常规控制心力衰竭治疗情况下,分析贫血对其心功能分级和肾功能的影响。结果随着贫血程度增加,心脏射血分数下降（P〈0.05）;CHF时肾功能障碍发生率为35.6%;随着心脏射血分数的下降,肾功能障碍亦逐渐增加且程度加重（P〈0.05）。反映肾功能的各项指标随贫血严重程度的加剧,恶化更加明显（均P〈0.05）。结论老年CHF合并贫血的患者心功能和肾功能障碍恶化明显,且贫血的程度越重,其病情也越严重,预后越差。     

Supraventricular arrhythmias in noncompaction of left ventricle: is this a frequent complication?

Despite growing recognition of the frequent presentation of cardio-renal syndrome, its underlying pathophysiology is not well understood, and no consensus as to its appropriate management has been achieved. On the other hand, there is growing evidence that the presence of anemia can worsen cardiac function and symtomps in patients with congestive heart failure (CHF) and that correction of anemia may beneficial. We believe that the treatment modalities, especially eryhtropoietin, to correct anemia will be an important part of our therapeutic armemanterium in the battle against CHF.     

Anemia in chronic kidney disease and congestive heart failure

Anemia is seen in chronic kidney insufficiency (CKI), dialysis patients, congestive heart failure (CHF), and renal transplantation. Anemia can lead to progressive cardiac damage as well as progressive renal damage. It is not generally appreciated that CHF itself may be a very common contributor to both the production of anemia as well as to the progression of the renal failure. Correction of the anemia with erythropoietin and, as necessary, intravenous iron, may prevent the deterioration of both the heart and the kidneys. We suggest that there is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other. We call this syndrome the cardio-renal anemia (CRA) syndrome. All physicians, especially cardiologists and internists who treat CKI and CHF, should be made aware of the dangers of anemia in CKI and CHF and should work with nephrologists to correct it.     

Myocardial disease, anemia and heart failure

Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, very poor quality of life, end stage renal failure, or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these patients is the fact that they are often anemic. The anemia is due mainly to renal failure but also to the inhibitory effects of cytokines on the bone marrow. Anemia itself may further worsen the cardiac function and make the patients resistant to standard CHF therapies. Indeed anemia has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, higher doses of diuretics, worsening of renal function and reduced quality of life. In both controlled and uncontrolled studies the correction of the anemia with erythropoietin (EPO) and oral or IV iron is associated with improvement in all these parameters. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia. Anemia may also play a role in the worsening of coronary heart disease even without CHF.     

慢性心力衰竭患者贫血与肾功能和神经内分泌细胞因子的关系

目的探讨慢性心力衰竭(CHF)患者贫血与肾功能和神经内分泌细胞因子之间的关系。方法对入选的121例CHF患者测定血红蛋白(Hb)、肾功能、TNF-α、可溶性细胞间黏附分子-1(sICAM-1)、白细胞介素-6(IL-6)、血管紧张素Ⅱ(AngⅡ)、NO、内皮素(ET)的变化;超声心动图测量LVEF,评价心功能;按Hb水平分为贫血组(47例)和非贫血组(74例)。结果随着心功能恶化,CHF患者LVEF和Hb水平逐渐降低,而尿素、肌酐(Cr)、血尿酸(BUA)水平明显增高(P<0.01);贫血发生率为38.8%,肾功能障碍发生率为24.0%,随着LVEF下降,贫血和肾功能障碍逐渐增加且程度加重(P<0.05)。贫血组患者血清TNF-α、sICAM-1、IL-6、AngⅡ、NO、ET水平明显高于非贫血组(P<0.01)。Hb和LVEF与尿素、Cr、BUA呈负相关;Hb与TNF-α、sICAM-1、IL-6、AngⅡ、NO、ET呈负相关,而与LVEF呈正相关(P<0.01)。结论CHF患者机体存在细胞因子的过度表达和肾素-血管紧张素系统的过度激活及伴随肾功能的降低,可能导致了CHF患者贫血的发生,且贫血也参与并加重了CHF发生发展的病理生理过程。     

The importance of anemia and its correction in the management of severe congestive heart failure

About half of all the patients with CHF are anemic (they have a hemoglobin of < 12 g%). The prevalence and severity of this anemia increase with increasing severity of the CHF. The anemia is caused by a combination of poor nutrition, associated renal insufficiency causing inappropriately low Erythropoietin (EPO) levels, bone marrow depression and EPO resistance caused by excessive TNF alpha and other factors, gastrointestinal blood loss caused by aspirin, ACE inhibitors, EPO loss in the urine with proteinuria, and hemodilution caused by the excessive plasma volume. Studies have shown that the anemia is an independent risk factor for death in CHF, almost doubling the mortality rate. Correction of the anemia with subcutaneous EPO and IV iron improves cardiac function and functional capacity, helps prevent the progression of renal failure, markedly reduces hospitalization and diuretic doses, and improves self assessed quality of life. This so-called Cardio Renal Anemia Syndrome is very common in CHF. Its successful treatment demands close cooperation between cardiologists and nephrologists.     

Therapy insight: congestive heart failure, chronic kidney disease and anemia, the cardio-renal-anemia syndrome

Congestive heart failure (CHF) and chronic kidney disease (CKD) often progress to end stage even with optimum medical therapy. One factor that is common to both conditions is anemia, which is present in about a third of CHF patients. CHF can cause or worsen both anemia and CKD, and CKD can cause or worsen both anemia and CHF. Thus, a vicious circle exists between these three conditions, with each causing or worsening the other. We have called this condition the cardio-renal-anemia syndrome. Anemia in CHF is associated with increased mortality and hospitalization, reduced cardiac function and evidence of more severe CHF and CKD than in nonanemic patients. Intervention studies in anemic CHF patients have shown that optimum medical treatment of CHF and the correction of the associated anemia with subcutaneous erythropoietin and oral iron or intravenous iron sucrose can improve cardiac function, patients' functional status, renal function and quality of life, and reduce the frequency of hospitalization and the dose of diuretics required.     

Heart rate response to graded exercise correlates with aerobic and ventilatory capacity in patients with heart failure

BACKGROUND: Autonomic dysfunction and reduced exercise tolerance are typical features of patients with congestive heart failure (CHF). Baro-chemoreflex balance and organ response may have a common role in conditioning exercise tolerance, ventilation, and chronotropic competence in patients with CHF. HYPOTHESIS: We tested the hypothesis that there is a relationship between functional capacity and chronotropic competence to exercise in CHF. METHODS: In all, 48 stable outpatients with CHF (age 65 +/- 10 years, 41 men, NYHA class 2.1 +/- 0, ejection fraction 31 +/- 7%, peak VO2 16 +/- 4 ml/kg/min) performed cardiopulmonary exercise testing (CPX). Heart rate (HR) response to exercise was assessed by the chronotropic index (CRI). The CRI was calculated by the following formula: CRI = peak HR - rest HR/220 - age - rest HR x 100 (normal value > 80%). The relationship of CRI to peak oxygen consumption (VO2) and ventilation/carbon dioxide production (VE/VCO2) ratio was examined. A group of 33 healthy controls underwent CPX as well. RESULTS: The CRI correlated directly with peak VO2 (r = 0.638, p < 0.001) and inversely with VE/VCO2 (r = -0.492, p < 0.001) in patients with CHF. A CRI < 78% identified patients with CHF and a peak VO2 < 20 ml/kg/min, area under the receiver operating curve (AUROC): 0.76, 95% confidence interval (CI) 0.60-0.92. A CRI < 74% predicted exercise hyperventilation in CHF (AUROC: 0.71 for VE/VCO2 > 30, 95% CI 0.53-0.88). The CRI was not significantly related either to peak VO2 or to VE/VCO2 in the control group. CONCLUSIONS: In patients with mild to moderate CHF, CRI correlates with functional capacity. This relationship adds new data on pathophysiologic grounds and supports the routine incorporation of CRI into CPX interpretation.     

早期纠正贫血对慢性肾衰竭心血管病变影响的多中心临床研究

目的观察早期使用促红细胞生成素治疗贫血对透析前慢性肾衰竭(CRF)患者心血管病变的影响.方法采用多中心、前瞻性、对照临床研究.血肌酐(Scr)在147～400 μmol/L的CRF患者158例,按基线Hb水平分组.将Hb<110 g/L的患者分为2组,(1)治疗组86例,每周接受α-促红细胞生成素100～135 U/kg皮下注射;(2)对照Ⅰ组40例,未接受α-促红细胞生成素治疗;将Hb≥110 g/L的32例患者作为对照Ⅱ组,未接受α-促红细胞生成素治疗.行超声心动图检查,测左心室质量指数(LVMI)、血压等,随访时间2年.结果 3组患者基线临床资料(年龄、性别、原发病、营养状况、高血压的发生率、使用降压药物的种类和数量等)无明显差异(均P>0.05);治疗组、对照Ⅰ组、对照Ⅱ组患者左心室肥厚(LVH)的发生率分别为72.1%、72.5%、59.4%;LVMI与Hb水平呈负相关(r=-0.70, P<0.01),与Scr呈正相关(r=0.64, P<0.05).治疗24个月后,治疗组患者Hb水平较基线时明显上升(P<0.05),LVMI较基线时明显下降(P<0.05),LVH的发生率(55.8%)较治疗前降低16.3%,但平均动脉压、使用降压药物的数量与基线相比无明显差异.对照Ⅰ组与对照Ⅱ组患者Hb逐渐下降,LVMI明显增加,LVH发生率与基线相比明显增高(P<0.05).随访期间,Scr较基线增高1倍的患者比率,治疗组(3.4%)与对照Ⅰ组(15.0%)相比差异有统计学意义(P<0.05),而对照Ⅰ组与对照Ⅱ组(9.4%)相比无明显差异(P>0.05).结论轻中度CRF患者存在LVH,贫血是导致透析前CRF患者LVH的重要原因.用促红细胞生成素早期治疗贫血能使部分患者LVH逆转.透析前CRF患者用促红细胞生成素治疗并不加重高血压,并可能有助于延缓肾衰竭的进程.     

Cardiorenal anemia syndrome: do erythropoietin and iron therapy have a place in the treatment of heart failure?

The cardiorenal anemia syndrome in congestive heart failure (CHF) is an independent risk factor for vascular morbidity and mortality. Several factors play a role in the pathogenesis of anemia in CHF, including inflammation, impaired renal function, use of certain antihypertensive or cardioprotective agents, and gastrointestinal or urinary losses of essential hemopoietic factors. Several trials evaluated the effects of administering erythropoietin (EPO) and/or iron to patients with CHF. Even though most of them were uncontrolled studies, their results suggest that EPO treatment might be beneficial in CHF. Nevertheless, more studies are needed and certain issues should be resolved, particularly the optimal hemoglobin level, before EPO can become part of the treatment of patients with CHF.     

充血性心力衰竭性贫血的研究进展

贫血在充血性心力衰竭患者中是常见的,发病率从4%到55%不等。其发病机制可能与血液稀释、营养不良、肾功能不全、炎症性免疫激活等因素有关。贫血与充血性心力衰竭患者的临床预后密切相关,并被认为是心力衰竭患者临床预后不良的独立因子。应用促红细胞生成素和静脉铁剂成为治疗充血性心力衰竭性贫血的新靶点。